The overall objective of this proposal is to develop a tomographic system which will allow accurate measurements of radiotracer biodistributions. We plan to concentrate on regional cerebral blood flow measurements using N-isopropyl I-123 p-iodoamphetamine and must, therefore, overcome the problems inherent in using I-123 labeled compounds. This will require alterations in our Harvard scanning multidetector emission computed tomography system, in our opinion the most promising instrument for single photon emission computer tomography. Three of these systems are currently in our laboratories. Our specific aims include improvement in the Harvard scanning multidetector tomographic brain system by increasing angular sampling, improving the collimators and improving attenuation correction; comparing the multidetector system with the rotating gamma camera through performance testing; determining the accuracy with which we can quantitatively measure activity distributions of I-123 in computer simulations of the regional variations in activity anticipated in the brain; comparing the accuracy of regional cerebral blood flow measurements using the percent injected dose of isopropyl I-123 iodoamphetamine with the modified Saperstein method introduced by Kuhl et al; determining the effect of agonists to the various brain receptors on the uptake of the radiotracer in the brain; and determining the extent of altered perfusion in patients with focal cerebral ischemia and with evolving and completed stroke. The later aspect of the study will be particularly important because it will determine the effectiveness of medical and surgical managements aimed at salvaging reversibly ischemic cerebral tissue. In addition, we will determine the prognostic importance of cerebral blood flow measurements early on in patients with acute cerebral ischemia and infarction.